Tezspire: which tox species, and why?

“Cynomolgus monkey was selected as the pharmacologically relevant animal model for non-clinical safety assessment”

“based on tezepelumab binding to human and cynomolgus monkey TSLP with picomolar affinity (KD vales of 15.8 pM and 32.2 pM, respectively)”

“Because of the lack of binding of tezepelumab to mouse TSLP, M702, a mouse surrogate antibody was developed for in vivo studies.”

“As tezepelumab only binds human and cynomolgus monkey TSLP, cynomolgus monkey represents the only suitable species to investigate the toxicology of tezepelumab.”

“In the maternal, embryo-fetal, and neonatal toxicity (ePPND) study, pregnant female cynomolgus monkeys were dosed Q7D at 50 or 300 mg/kg IV from early gestation through delivery.”

“The conduct of carcinogenicity studies in rodents was not feasible as tezepelumab does not bind to rodents’ TSLP.”

“Of this total, ten studies were non-clinical pharmacology studies (including in vivo models using a murine surrogate anti-TSLP mAb, M702) and one study was a safety pharmacology study, which is described together with the non-clinical pharmacology reports.”